Thrombolysis or peripheral arterial surgery: phase I results. TOPAS Investigators

Area of Science:

• Vascular Surgery
• Interventional Radiology
• Thrombolytic Therapy

Background:

• Thrombolytic therapy is a common treatment for peripheral arterial occlusion.
• Prospective, randomized comparisons between thrombolysis and standard surgical therapy are limited.
• The Thrombolysis or Peripheral Arterial Surgery (TOPAS) trial aimed to compare recombinant urokinase (rUK) with surgery for acute lower-extremity ischemia.

Purpose of the Study:

• To conduct a dose-ranging trial evaluating the safety and efficacy of three rUK dosages against surgery.
• To determine the optimal rUK dosage for treating acute lower-extremity ischemia.
• To compare patient outcomes, including mortality and amputation-free survival, between rUK and surgical interventions.

Main Methods:

• A multicenter, prospective, double-blind study randomized 213 patients with acute lower-extremity ischemia.
• Patients received catheter-directed rUK at 2000, 4000, or 6000 IU/min, or underwent surgery.
• Follow-up was for 1 year, with data analyzed on an intent-to-treat basis.

Main Results:

• The 4000 IU/min rUK dosage demonstrated the best balance of efficacy and safety, achieving 71% complete thrombus lysis.
• Hemorrhagic complications were significantly lower in the 4000 IU/min group (2%) compared to lower and higher doses (13% and 16%).
• One-year mortality (14% vs 16%) and amputation-free survival (75% vs 65%) did not differ significantly between the 4000 IU/min rUK and surgical groups, with reduced need for surgery in the rUK group (p < 0.001).

Conclusions:

• An initial rUK dose of 4000 IU/min is a safe and effective treatment for acute lower-extremity ischemia.
• rUK therapy offers comparable limb salvage and patient survival rates to surgery.
• rUK treatment can decrease the requirement for complex surgical interventions following thrombolysis.